The future belongs to those who believe in multiplex CAR T engineering

Laura Volta1, Chiara F Magnani1

  • 1Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.

Cell Stem Cell
|July 4, 2025
PubMed

Insights

Engineered induced pluripotent stem cell-derived CAR T cells overcome toxicity and immune evasion, improving treatment for HER2-positive solid tumors by enhancing tumor targeting and persistence.

Area of Science:

  • Oncology
  • Immunotherapy
  • Stem Cell Biology

Background:

  • CAR T-cell therapy faces challenges in HER2-positive solid tumors due to toxicity and immune evasion.
  • Existing treatments are limited by the tumor microenvironment and antigen escape.

Purpose of the Study:

  • To develop an induced pluripotent stem cell (iPSC)-derived CAR T-cell product for improved solid tumor treatment.
  • To engineer CAR T cells for tumor-selective targeting, enhanced persistence, and overcoming immune evasion.

Main Methods:

  • Generation of iPSC-derived CAR T cells.
  • Engineering for tumor-specific antigen recognition.
  • Enhancement of resistance to the immunosuppressive tumor microenvironment.
  • Optimization for improved cell persistence and trafficking.

Main Results:

  • The engineered iPSC-derived CAR T cells demonstrated tumor-selective targeting.
  • Enhanced resistance to the immunosuppressive tumor microenvironment was observed.
  • Improved cell persistence and trafficking within the tumor were achieved.
  • Mitigation of antigen escape was a key outcome.

Conclusions:

  • iPSC-derived CAR T cells offer a promising platform for overcoming challenges in solid tumor immunotherapy.
  • This engineered cell product shows potential for more effective treatment of HER2-positive solid tumors.

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